The goal is to understand the molecular mechanisms of sugar transport by transmembrane proteins. Transport is largely achieved by a family of proteins which span the membrane 12 times. Two transporters have been selected from this family: the human erythrocyte glucose transporter (Glut1) and the E. coli glucuronide transporter (GusB). Glut 1 is a ubiquitous facilitative glucose transport protein in humans, abundant in erythrocytes and in the brain, providing these tissues with glucose, their primary energy source. GusB is the protein responsible for transporting glucuronide sugars into the E. Coli bacterium in the human intestine. The aim is to determine the structure of these proteins in order to understand their transport mechanisms. Large, highly ordered two- or three-dimensional crystals are required for structural determination of transmembrane proteins. Such crystals can only be grown from protein-lipid-detergent complexes that are homogenous. To this end, the investigators have purified Glut1 and GusB in ten-milligram quantities, and have found conditions to keep these proteins active, stable, and monodisperse. They are applying and developing novel methods for their crystallization. Cryo-electron microscopy, electron diffraction, and x-ray crystallography will be employed to determine the protein structure from such crystals. Knowledge of the structure of these proteins and their conformational changes will reveal their transport mechanisms. In addition, these structures will become paradigms for other members of the 12-transmembrane helix transporter family, including the glucose transporter in muscle and fat tissues (Glut4), which is involved in the pathogenesis of type II diabetes, and the dopamine transporter responsible for cocaine addiction.